Yves here. Evidence is mounting that the US and other advanced economies are failing to provide adequate levels of what have come to be considered essential services, like reliable power, clean water, and now, adequate medical care. Rural hospitals are closing. Diabetes drugs are so wildly overpriced that many Americans try to get by on low or intermittent doses. Primary care doctors are too few.
Covid supply chain disruptions hit many categories of medications, from Adderall to some antibiotics to children’s Tylenol. As this article describes, the shortage of cancer medications is a potentially lethal threat to many patients. Yet despite experts warning for some time of US dependence on Chinese (and to a lesser degree Indian) active ingredients and end products, the US has not done anything to build buffers.
One simple idea to investigate is testing the shelf life of products and authorizing pharmacies to sell them after their official sell by date up for a specified period when a drug is designated as in short supply. My understanding is that most medications retain their potency for roughly a full year after their sell by date. It would presumably not be hard or costly to test potency for at least pretty widely used medications. This could be an important stop-gap until longer-term solutions are put in place.
By Arthur Allen, KFF Health News Senior Correspondent, previously worked at Politico, and before that, a freelance writer for publications such as The New York Times, The Washington Post, Smithsonian, Lingua Franca magazine, The New Republic, Slate, and Salon, and had worked for The Associated Press for 13 years. Originally published at KFF Health News
On Nov. 22, three FDA inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, attention-deficit/hyperactivity disorder pills, blood thinners, and antibiotics. Covid-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures — undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, an oncologist in Hot Springs, Arkansas, who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during covid; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The 10 cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives — though sometimes less effective and often with more side effects — are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Brent McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family — his other daughter, Cate, made a TikTok videoabout her sister’s plight —were simply stunned at such a basic flaw in the health care system.
At Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Moore and her colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale — only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics Manufacturers Are Pulling Out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big buyers, including wholesale purchasers Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett Co., with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Sardella, the Washington University professor, testified last month that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited two months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-milligram bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at Moore’s clinic.
“It’s hard to have these conversations with patients — ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, chair of the Department of Obstetrics, Gynecology and Reproductive Health at Rutgers New Jersey Medical School.
Should Government Step In?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm, she said. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Virginia, that will produce dozens more, Coukell said.
Ratain and his University of Chicago colleague Satyajit Kosuri recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store two years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
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For profit healthcare
Not a bug but a feature
True. In the US we don’t have “healthcare” we have private health insurance and BigPharma oligopoly.
It is Health Extortion, not health care.
‘Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.’
Looked those two drugs up, both are platinum-based… then looked to see the word on the global platinum supply, it’s likely countries of origin and most common uses. Chemo drugs were not in the Top 5, the current demand for the Top 5 though would be huge.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146684/
https://investingnews.com/wpic-platinum-market-forecast/
https://www.wsj.com/livecoverage/stock-market-today-dow-jones-05-15-2023/card/platinum-market-seen-near-million-ounce-deficit-amid-supply-shortage-ylUAVdxEiTCmdnH1WlRZ
https://en.wikipedia.org/wiki/Platinum
Per drugs.com, maximal therapeutic dosage of Cisplatin is “100 mg/m^2 by slow IV infusion”. Those units had me a bit befuddled, as I was expected something like mg of Cisplatin per kg body weight. Found the explanation here:
https://onlineconversion.vbulletin.net/forum/main-forums/convert-and-calculate/5583-iv-dosage-units
“many chemotherapy drugs are dosed based on body surface area (BSA). This was just established a long time ago asumming that the patient with a larger BSA would also have larger organs etc for the drug to get cleared through. Today, actually, it can be determined that the clearance of these drugs are not actually related to BSA, but many are still dosed that way.
Therefore, the mg/m^2 is actually mg per body surface are of your patient. The adult average is about 2.2 m^2 but there are formulas using height and weight to calculate BSA.”
So let’s say our dose is 50 mg/m^2, times 2 m2 gives 100 mg Cisplatin per dose. Molar mass of Cisplatin is 300 g/mol, of which around 2/3 are due to the Pt atoms, so we’re talking less than 100 mg Pt per dose, costing on the order of $5 based on recent Pt prices. I was unable to quickly find data on annual Pt usage in anticancer drugs, but using a surely-wildly-generous number of 1 billion 100 mg dosages per year translates to 100 tonnes per year, which would be quite significant, of similar order as the #1 consumption category, vehicle emissions devices. Wkikipedia provides a much tighter upper bound:
“Of the 218 tonnes of platinum sold in 2014, 98 tonnes were used for vehicle emissions control devices (45%), 74.7 tonnes for jewelry (34%), 20.0 tonnes for chemical production and petroleum refining (9.2%), and 5.85 tonnes for electrical applications such as hard disk drives (2.7%). The remaining 28.9 tonnes went to various other minor applications, such as medicine and biomedicine, glassmaking equipment, investment, electrodes, anticancer drugs, oxygen sensors, spark plugs and turbine engines.” [I’m guessing “investment” = bullion.]
Using the cancer cases/year number you provide indicates on the order of several million doses per year – call it 10 million, translating to O(1 tonne/year). Thus global production seems not an issue for Cisplatin manufacturers.
I wasn’t thinking about amounts* when I posted so much as the politics of distribution… it’s like food historically, we produce enough globally for now but the politics of getting it where its needed is intense, and there’s more competition than ever. Not the ingredient per se but the system it gets moved around in.
In the Superpowers of Tomorrow, where does South Africa figure in? If there’s already a platinum supply shortage, how well can chemo drugs compete with other demand uses, like catalytic converters? Electric cars made with tons of raw rare minerals (the climate crisis) or maintenance chemo doses for old people or those with late stage cancers (life extension)? What will governments prioritize? I think I know how Lambert would reply.
‘The 10 cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives — though sometimes less effective and often with more side effects — are available. But some doctors are even rationing doses intended to cure.’
*A nifty bit of math prestidigitation there, ewmayer. I was impressed.
Actually, if platinum drugs are easy to produce, and we stockpile them, the platinum from expired doses can be recycled and the cost modest. 100 mg platinum is perhaps 3-5 dollars, and many generics cost 1 dollar or much less, therefore I think this may be the case.
Platinum therapies and combination therapies that include those drugs are indeed very frequent.
I was under the impression that India is a major manufacturer and supplier of Generic Drugs.
Or is that poor understanding on my part?
I think this is true, but India actually sources many of the active ingredients from China.
Fits neatly into the neo-liberal hurry-up-and-die plan.
How much did these companies participate in stock buy backs leading up to these difficult times – how much of the boards of directors have been hopping over from one company to the other… just curious to see the debt loading dynamics on these producers
“curious to see the debt loading dynamics on these producers”
Do you mean “these murderers” ?
Thanks for making this the late post. I prefer screaming at my computer after I’ve finished my coffee.
https://www.drugs.com/drug-shortages/
Seems fine.
“We got them vaccinated, kept them safe, ”
Do they not see the connection ? – Got them vaccinated because they were told to and as medical employees that’s the main thing they know how to do: follow orders.
“Kept them safe” – They have no idea if any of it is safe. The data suggests strongly that it wasn’t safe, but no one is allowed to ask the question.
Everyone is on there own. It’s all back to 3 score and 10 and learn how to take care of yourself.
A second attempt:
Oversharing here, but a year ago my current (and I hope, future) health depended on cisplatin. This is an outrage of the first magnitude. But according to President Biden, nothing will fundamentally change…Thanks, Mr. President!
Or as I have put it previously: Deindustrialization, an obligate correlation of which has been the near-total loss of control of the real economy, despite a surge in paper profits leading to an income distribution mimicking that of the late-1920s. We all know how that turned out in a world that was not yet full.
Because markets, die faster. A feature not a bug! Indeed.
The government had zero problems with funding the research and development of these drugs. We should be supporting organizations that manufacture necessary drugs in the US.
but the big drug corps(e) feel put upon:
https://thehill.com/policy/healthcare/4058317-drug-industry-launches-furious-legal-fight-against-medicare-negotiating-powers/
system selects for psychopathy, and i figger we’re approaching peak psychopathy, at home and abroad.
after being in the front row for my late wife’s cancer adventure, i decided pretty quickly that i’d go gently into that good night.
zero healthcare, save out of pocket.
my healthcare plan is growing much of what i eat, and avoiding crowds from october to march.
i hate my country.
If your unfortunate enough to have to get your medical treatment here in the US, you are either wealthy and have a good insurance policy or you are not wealthy and have insurance with high deductible and thus unaffordable treatments. You can always buy the drugs at 100x the standard global price (either extorted generic or extorted brand name) or following Lamberts neo-liberal rules “go die”, “because markets”. Medicine is probably one of the areas where those rules are the most apparent.
But what exactly is the policy decision? Isn’t the root policy decision to have a weaker government so that private industry can get their chance to do “everything” (that’s profitable) and government just stands by to bail them out or mop-up on poor population health outcomes. Otherwise, according to the prevailing ideology, we’d be doing socialism, nasty socialized medicine, which some are equating with evil democracy.
Yves:
While I’m all for this, I can only imagine that it would instantly be used to further tighten up supply chains, because manufacturers would come to rely on that one year buffer. There would be a temporary buffer and sigh of relief, and the eventual tightening again because God forbid there be any slack in the system when there’s profit to be made. Everyone would end up being on meds that were a year or less from losing their actual efficacy, and it would only be a matter of time before people ended up sick or dead because the drugs were expected to work.
It really isn’t a bad idea, though, in the face of what we’ve got. There would just need to be some real teeth when someone tries to sell drugs past the 1 year mark. The true solution is to nationalize it all and Single Payer the health care system into submission, but that’s just paint fume dreams.
This seems to be an excellent case for a drug manufacturer to be set up under government charter focused on generics.
The government can provide start-up capital and establish a firm devoted to manufacturing critical drugs like insulin and the cancer drugs mentioned here. It on-shores the manufacturing and it can be self-funding selling drugs at basically cost of production.
There are precedents. Fannie Mae, addressed the market failure of no one willing to fund 30 year mortgages, and operated for years as a company with a government charter. (Its failure was, at its root, a decades-long growing failure of regulation.)
Now we have a market failure that is killing people not just stopping them from borrowing money.
But as long as it’s the “free market” I guess we have no choice.
This sounds fine, but there are thousands of pharmaceutical compounds and even more medications, so there is a necessity for private suppliers too. On top of that, here we also have a problem with American oligopoly of distributors of medications, in this instance, forcing cost-cutting without inspecting what the low bidder does.
Quality is an inherent problem when you go for low bids, e.g. why so many municipalities around the globe have such crappy roads — you need to have quality specs AND check them, in this case, what is there under shiny pavement surface. But there are strong pressures to cut corners to meet budget constrains or profit goals (that may be excessive). All too often, the results are deadly, houses pancake during earthquakes (and even without), medicines poison people or are ineffective and so on, and in the most recent example, a submersible implodes (did anyone tested it without folks on board at 4000 m depth?).
In the case of pharmaceutical compounds and final products, inspecting the quality is an international problem that requires international solutions. In the example from this article, India has cancer patients too, and so does China etc., and uniforms minimal adequate standards, and methods of checking them, should be developed regardless on conflicts between the countries on different matters.
Cisplatin is a dramatic example, but as described here, this is a general issue for all generic drugs, and the main cause seems to be the oligopoly of wholesalers. Once the market is reduced to few players, they just need to observe a simple etiquette to squeeze the consumers or suppliers (or both, in the case of wholesalers).
A peculiar situation in the drug market is that the volume comes from mostly from cheap stuff, and the revenue, mostly from expensive drugs. If wholesalers squeeze the producers so much that they drop products, the bottom line is not affected too much. Initially, it work fine because the producers sell in combined packages, partially because of the cost of closing/opening production lines, partially because of the pressure to sell an entire menu of drugs. And then poof, one supplier after another goes out of business.
The opposite distortion happens to. The access to American market is cumbersome for generics, creating numerous cases of supply side monopolies and ridiculously high profit margins. Anti-trust laws were supposed to eliminate such effects, but in recent decades, USG is oblivious to monopoly issues, enforcers and courts defining them narrower and narrower.
This seems like a problem the Sackler Family could take on as part of the restitution owed the survivors of their Narco-terrorism.